DESCRIPTION: NMDA receptor antagonists may possess therapeutic utility for a variety of CNS pathologies, but NMDA receptor antagonists may elicit side effects including PCP-like psychotomimetic episodes. Early Araxin compounds discovered at NPS antagonize NMDA receptors at a unique site and by a novel mechanism, possess therapeutic utility in animal models of CNS disease, and do not elicit a PCP-like behavioral profile in rodents. Hypotension, elicited by early Araxin compounds, however, halted their further development. NPS has recently discovered a new class of compounds, based on the early Araxin compounds, but simplified chemically, which retain high potency against NMDA receptors. The compounds, exemplified by NPS 846, are termed "NPS 846 generation Araxin compounds". Preliminary results demonstrate that NPS 846 possesses anticonvulsant and neuroprotectant activity, but does not elicit cardiovascular effects or PCP-like behaviors. The proposed studies will confirm and expand upon these preliminary findings.